2-thio-4, 6-diamino-1, 3, 5-thiadiazine and salts thereof



Patented Mar. 26, 1946 2-THIO-4,62DIAMINO;1,3,5+THIADIAZINE= AND SALTS THEREOF No Drawing. Application August 24; 1943; Serial'No. 499,824

9 Claims. (Cl. 260-e-251). i

This invention relatesto newbrganic .compounds and their m-eparatio'n.-;- -:niore. particularly to 2-thio-4 6-diamino 1,3,5-thiadiazine, its tauto: mersg'and'acidsalts thereof.

Thecompounddescribe'dandclaimed hereinby mixtures of water with thesehsolvents, etc. 'It is us and designated as 2-thio-4,6-diamino-1,3;5; also soluble in concentratedsolutionsof strong thiadiazine is believed to have the fOllOWing strucacids from which it may be recovered as an'acid tural formula: salt. The'compound may be dissolved in solution S of alkalies but in so. doing; its molecular structure 1 10 is very materially rearranged. to form alkalimetal .v w cyanoguanidoclithiocarbonates;; The N compounds of the presentinvention are useful particularly as intermediates in thepreparation 1 of dithioammelide ;.and. guanylt'hiourea. Other useful organic compounds mayheprepared from Ch ca d p ys a prop rti s of the m the compounds of theJpresent invention. I poundindicate th-at-dt may-also existiinwhole Z-thio.. 4 6-djaminga1 3;5;th1adiazj ne b or in part-,in one or more tautomericfonnsunder prepared by' treating an alkali t w certairrconditions; -One such-tautomeric form guanidQdithiOcarbQnate ac1d1 ;m t ri -1, aybe as follows: i Theiacidicmaterial may bea strong mineral acid s suchas, hydrochloric acid, sulfuric acid, phos- NHrQ phoric acid, or thelike, or it may bean organic u acid such as formic acid, acetic acids-chlorpro- N pionic acid, benzoic acid, p-toluenesulfonic'acid, c or the like. Aqueous solutions of compounds such IQIH as carbon dioxide, hydrogen sulfide, zinc chloride, aluminumlsulfate and thelikezare. also sufliciently m wtmoshydrm acidicto convert alkali metal u-cyanoguanidodi- Amther thiocarbonatesninto 2-thio=4,6.-,diamino=1,3,5-thislble tautomenc form as follows: "a'diazinei Surprisingly:enoughwsuchcacidicv salts S v astzinc (chloride. and; aluminum sulfate precipiniN o c-srrtate-2-thioF4,6-diamino=1,3,5.-thiadiazine and: do

It notiorm the zinc oralmninumlsaltsof m-cyano- N, guanidodithiocarbonic acid. .Aecordingly we use 0 the-termffacidiccmaterial? hereinaftermto include all of these different :types andlkinds. of acidic This. form may .be' named z-thiolel-imino-fiamino=1, 3,5;thiadiazinei Several other possible configurations could also .belpostulated, However, the structure firstrrepresented is; believed .to be the 'most likel istructure of .our new com.- pounds and is being claimed herein with the understanding that, tautomeric forms of thecompound are to be considered as falling within the purview-wt ourinventioi'iy v 'Iau'tomerism in compounds :iof 'this type :is a common. :phenomenon known-to chemistsza;

tures as highas 360C. andmd'ecomposing;without melting "when heated at higher temperatures; It

is slightly soluble in 'water andsom-e-othersobvents; such "as, alcohol, celiosolve'; acetone'and materials.

In converting alkaliumetal; w-cyanoguanidodi thioc-arbonates to -'2-thio-4i61diamino-1,3 5-thiaF diazine in accordance i with 7 our invention; it is merely necessary to dissolve a suitable alkali metal w-cyanoguanidodithiocarbonate in water, or other. solvent, and'ua'dd: ran iacidicmaterial to the solution.-: 2-thio-v4;6+diaminoe1,3;5. thiadia, zine is immediately precipitated-as a" finely'crystalline, extremelybulkymass .-The reaction may be represented as follows:

2-thi0-4;6+diamino l,tigfithiadiazineis weakly Mes, NH H i basic in character and forms salts with organic 5 u HzN-C o=s and inorganic acids having a dissociation con- +2Me+ stant'flf at least? TX'IO. "r118 ;(flnfflpoln d occurs Mess. in the form of finecotton lik'e needles when 'reerystallized'fro'm-a large volume of water; It is surprisingly heat" stable, not melting at tempera- -Inthe" equation Me "TEPIB'SBIltS' -an-- alkali-metal "A slurry of 1260 and H+ is a hydrogen ion resulting from the presence of an acidic material in the reaction mixture. Because of the bulky nature of the precipitate, it is advisable that the reaction mixture be vigorously stirredto avoid occlusion of acidic'material by the bulky precipitate. Alsobecause of the.

nature of the precipitate, we prefer to use volatile acids such as acetic and hydrochloric which can. be removed from the product by heating.

Since the reaction proceeds easily and completely to yield the desired reaction product at room temperatures, we ordinarily prefer to corn duct the reaction by simply adding an acidic material in slight excess above the amounts indicated by the preceding equation to the solution of alkali metal w-cyanoguanidodithiocarbonate.

Temperatures within the range of C; to about;

40 C. may also be employed if desired.

Acid salts of 2-thio-4,6-diamino-1,3,5-thiadia zine maybe prepared bytreating the latter com-. pound with moderately concentrated solutions of strong acids. By strong acids, we mean those acids havin an ionization constant of 1X10- or greater. The salts are ordinarily prepared by merely mixing the thiadiazine withthe acid. The application of. heat may be helpful in some cases in dissolving ,thereactants. Ordinarily salt formation occurs at once-and the reaction can be considered complete ,within fifteen minutes. Cooling the resulting solution precipitates crystals, of the acid salt. We have prepared the sulruric acid, hydrochloric acid,.toluenesulfonic acid, phosphoric acid, formic acidfland salicylic acid this "method. Other strong acids may also be employed to form thiadiazinesalts. Our invention will now be illustrated bymeans of the following, specific examples in which 2,- thio-Yifi-diamino-1,3;5-thiadiazine is prepared in various-ways from potassium c-cyanoguanidodi thidcarbonata Other alkali-metal w-cyanmguanidodithiocarbonates may be prepared and converted to 2-thio-4,6-diamino'-1,3,5-thiadiazine in thesame manner.

' Example 1 1.19 g. of carbon disulflde was added to a stirred S pension of 24.4 g. o'fpotassium dicyandi amide in '200.ccgof' acetone; The mixture was then heatedto refluxing temperature. .Within a short time; the outer surfaceof the potassium dicyandamide crystals became yellow and the liquid ght yellow. in color. Refluxlng was continued salts of"2-thio-4,6-diamino-1,3,5-thiadiazine by I or 2. l hours. The mixture was cooled, and a pale yellow solid consisting of equimolecular" quantities of w-cyanoguanidodithiocarbonate and dicyandiamide was obtained upon filtration.

When the solid was dissolved in ice water and acidified with acetic acid,a precipitate of 2-thio- 4,0 dia mino-l,3,5-thiadiazine was obtained.

Example-2 f g. of dicyandiamidein 10 liters of acetone was-cooled to 0 0., 1955 g. of 85% notassiuinhydroxide pellets and 1000 cc. of carbon disulfide were then" added to the dicyandiamide solution with yig'orous stirring. Before long the temperature began to rise steadily and the slurry became pale yellow., After three,- fourths of an hourLthe temperature was 17 C. and the slurry had become a thick cream of the insoluble yellow product. After 2.5 hours at a temperature between 10 and 20 C., the product was filtered, reslurried in aliter of cold acetone,

filtered, washed with'acetone and dried. The

product was dipotassium w-cyanoguanidodithiocarbonate.

I To 1177 g. of dipotassium w-cyanoguam'dodithiocarbonate dissolved in 9 gallons of cold water was. added slowly with stirring 650cc. ct glacial acetic acid. As the acetic acid was adde'd, the solution became increasingly thick with a bulky white precipitate until at the neutral point the reaction mixture had'b'ecome a thick slurry. As t the acetic acid was added, the color of the slurry changed completely from a bright orange to a pale yellow color. The fiocculent solid Was centrifuged, and dried in an oven at 112 C., A

.yield of 616 gof 2-thio-4,6-diamino-1,3,5-thiadiazine was obtained. A sample of the product, after being recrystallized several times from water, gave the following analysis:

%o %H' %N %s Calculated for OIiHiNlSfl. -t I G-diamino-l,3,5-thiadiazine) 22. 50 2. 50 35.00 40.00 Found 22.95 2.76 34.81 39.97

The product is very heat stable and decomposes without melting attemperaturesabove 360 C.

7 Ea camplc 3 V Asolution of 23.6 g. of dipotassium w-cyanoguanidodithiocarbonate in 100 cc. of water was prepared and a solution of 13.6 g. of zinc chloride in 100 cc. of water. was added thereto at room temperature. A light yellow solid first precipitated which changed'rapidly into a nearly colorless cake. More water was added to the mixture 3 and'the solid filtered. Thebulk of the solid was then boiled with about 800 cc. of water. However,

a considerable amount of the material, probably zinc hydroxide, did not dissolve. Activated charcoal and filter aid were added v tothe mixture which was then filtered while hot. The undissolved solid was then extracted twice with two 800 cc. portions of hot water. As the combined filtrates cooled, colorless, needle-like crystals of 2-thio 4,6 diamino 1,3,5 thiadiazine formed.

commenced to form. Although the reaction appeared to be a neutralization reaction, the pH of thesolution remained above 7 throughout. The

product was.recovered by filtration and when analyzedhad the properties of 2,thio-4,6-diaminc-1,3,5-thiadiazine as described in the preceding examples. I

' Era mpleid r The above experiment was repeated using hydrogen sulfide gas instead of carbon dioxide as the acidic material. 2-thio-,6-'diamino-1,3,5- thiadiazine was precipitated as before.

7 7" 'ErcmpZe 6.

8 .g. A ;of powdered 2-thio-4,6-diamino-1,3,5-

thiadiazine was dissolved in 55 cc. of concentrated sulfuric acid and the orange colored solution poured over; ice. 'The resulting'solution was cooled in an ice bath and the yellow crystalline precipitate which formed was filtered, washed with dioxane and dried in a vacuum desiccator. The product, the acid sulfate salt of 2-thio-4,6- diamino-1,3,5-thiadiazine, had a melting point of 198 C.

Example 7 A slurry of 2-thio-4,6-diamino-1,3,5-thiadiazine in ethyl alcohol was refluxed with an excess of concentrated hydrochloric acid. After filtering and cooling the solution, the hydrochloride salt of 2-thio-4,6-diamino-1,3,5-thiadiazine crystallized.

Example 8 A slurry of 8 g. of 2-thio-4,6-diamino-1,3,5- thiadiazine and 13 g. p-toluene sulfuric acid monohydrate in 125 cc. of Water was heated to boiling and the insolubles filtered. On cooling, the p-toluene sulfonic acid salt of 2-thio-4,6- diamino-1,3,5-thiadiazine precipitated in the form of yellow plate-like crystals which decom posed when heated at 21822 C.

Example 9 Phosphoric acid (85%) was slowly added to a slurry of 8 g. of 2-thio-4,6-diamino-1,3,5-thiadiazine in 100 cc. of hot water until complete solution resulted. The yellow solution was filtered and after cooling yellow needle-like crystals of the phosphoric acid salt of 2-thi0-4,6diamin0-.

1,3,5-thiadiazine were obtained.

We claim: 7

1. Compounds of the group consisting of 2- thio-4,6-diamino-1,3,5-thiadiazine, its tautomers,

' and the acid salts of such compounds.

2. 2-thio 1,6-diamino-1,3,5-thiadiazine. -3. 2-thio-4,6-diamino-1,3,5-thiadiazine hydrochloride.

4. 2-thio-4,6-diamino 1,3,5 thiadiazine acid sulfate.

5. A method of preparing 2-thio-4,6-diamino- 1,3,5-thiadiazine which comprises mixing an alkali-metal w-cyanoguanidodithiocarbonate with an acidic material and recovering the thus formed 2-thio-4,6-diamino-1,3,5-thiadiazine.

6. A method of preparing 2-thio-4,6-diamino- 1,3,5-thiadiazine which comprises the step of mixing potassium w-cyanoguanidodithiocarbonate with an acidic material at a temperature within the range of 0 C. to C. and recovering the *thus formed 2-thio-4,6-diamino-1,3,5-thiadlazine.

bonate with acetic acid at a temperature within.

the range of 0 C. to 40 C. and recovering the thus formed 2-thio-4,6-diamino-1,3,5-thiadiazine.

DONALD W. KAISER. RUSSELL L. SPERRY. 

